PROJECT SUMMARY Glioblastoma (GBM) is the most common, aggressive and proliferative primary brain tumor in adults despite current therapeutic strategies that combine surgery, radio, and chemotherapy. The high invasive capacity of GBM makes total surgical resection virtually impossible, resulting in an extremely high recurrence rate. The ability to form a new tumor resides in a subpopulation of cells within the GBM called brain tumor initiating cells (BTICs). BTICs are undifferentiated cells with self-renewing and pluripotential capacity, with the added ability of forming tumors in vivo. Our group and others have reported that among primary GBMs, those located in close proximity to the lateral ventricles (LV) present multiple distinct features, including increased recurrence at distant locations, which negatively affect patients' survival. The cause for worse outcomes in patients suffering LV-proximal GBMs is not known. Possible explanations may involve the proximity of these tumors to the cerebrospinal fluid (CSF) and neurogenic niche in the sub-ventricular zone (SVZ). In a pilot study, we have determined that human non-cancer CSF repels BTICs migration in vitro. The molecules in the CSF responsible for this effect are not known. Here we propose to study the interactions between BTICs and different fractions of CSF. We hypothesize that CSF can induce a more aggressive behavior of GBM cells. We will perform this research using intraoperative human tissue. Upon completion of this study we will have gained a better understanding of the effects of CSF on GBM cells and will have discovered possible factors within CSF which influence BTICs and cancer progression. Ultimately, we hope to reveal specific targets for therapeutic intervention leading to increased survival in patients with GBM.